(Oxime)carbamoyl fatty acid amide hydrolase inhibitors
AssigneeBristol-Myers Squibb Company
InventorsSing-Yuen Sit, Kai Xie, Hongfeng Deng
Life of this patent
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Abstract
The present invention relates to novel oxime carbamyl derivatives and pharmaceutical compositions comprising said derivatives which inhibit fatty acid amide hydrolase. These pharmaceutical compositions are useful for the treatment of conditions which can be effected by inhibiting fatty acid amide hydrolase including, but not limited to, neuropathic pain, emesis, anxiety, altering feeding behaviors, movement disorders, glaucoma, brain injury, and cardiovascular disease.
Claims32
A compound of Formula I:
- 228
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein
- A is dibenzofuranyl, dibenzothienyl, naphthyl, indolyl, fluorenyl, carbazolyl, or represented by Formula II:
- 229
- wherein
- a is 1 or 2;
- R is C1-16 alkoxy optionally substituted with phenyl, pyridyl or morpholinyl;
- phenyl optionally substituted with C1-4 alkyl;
- phenoxy;
- phenyl-C1-4 alkyloxy-;
- pyridyloxy;
- pyridyl-C1-4 alkyloxy-;
- —N(H)—C(O)—C1-16 alkyl;
- or—C(O)—N(H)—C1-16 alkyl;
- R1 is a bond or a C1-3 branched or linear aliphatic hydrocarbon;
- and
- B is C1-4 alkyl, indolyl, benzofuranyl, benzothienyl, dibenzofuranyl;
- dibenzothienyl, fluorenyl, carbazolyl, naphthyl, quinolinyl or isoquinolinyl,
- wherein each is optionally substituted with one or more of the same or different substituent selected from the group consisting of C1-4 branched or linear aliphatic hydrocarbon, C1-4 alkoxy, halo, haloalkyl, nitro and (C1-3 alkyl)0-2 amino-;
- or represented by Formula III or Formula IV:
- 230
- wherein
- R2 is hydrogen, halo or C1-4 alkyl;
- R3 is C1-4 alkyl, pyridyl, halo, or phenyl optionally substituted with one or more of the same or different substituents selected from the group consisting of halo, C1-4haloalkyl and nitro;
- X is CH or nitrogen;
- R4 is C1-4 branched or linear aliphatic hydrocarbon, C1-4 alkoxy, halo, haloalkyl, nitro or amino;
- and
- b is 0 to 3,
- provided that
- if R2 is halo, then R3 is not halo;
- and if R3 is halo, then R2 is not halo.
A compound of Formula VI:
- 238
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein
- a is1;
- R is C1-2 alkoxy;
- R2 is hydrogen or methyl;
- and
- R3 is methyl, pyridyl, phenyl optionally substituted with one or more halo, haloalkyl or nitro.
A compound of Formula VII:
- 239
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein
- a is 1;
- R is C1-12 alkoxy;
- R4 is halo;
- X is CH or nitrogen;
- and
- b is 0 to 2,
- with the proviso that when X is nitrogen then b is 0.
A compound of Formula VIII
- 240
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein
- a is1;
- R is C1-12 alkoxy;
- R1 is a C1-3 branched or linear aliphatic hydrocarbon;
- R4 is phenyl, C1-3 alkoxy or halo;
- X is CH or nitrogen;
- and
- b is2.
A compound of Formula IX:
- 241
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein
- a is 1;
- R is C1-12 alkoxy;
- R1 is a C1-3 branched or linear aliphatic hydrocarbon;
- and
- X is CH or nitrogen.
A method of treating a condition or disorder by inhibiting fatty acid amidohydrolase in a mammal comprising administering to the mammal a therapeutically effective amount of a represented by the formula:
- 242
Dependencies are inferred from the claim text.